Biomedical subjects

Tülay Akçay

Publications and source records attributed to Tülay Akçay.

14 recordsLinked to original sources

PubMed2005

Significance of the O6-methylguanine-DNA methyltransferase and glutathione S-transferase activity in the sera of patients with malignant and benign ovarian tumors.

OBJECTIVE: To demonstrate O6-methylguanine-DNA methyltransferase (MGMT) and glutathione S-transferase (GST) activities by analyzing the sera separately obtained from patients with malignant ovarian tumors, benign ovarian tumors, and healthy individuals. STUDY DESIGN: Fourty-nine patients with ovarian cancer, nine patients with benign tumors, and 22 healthy women were included in this study. Blood samples were obtained from all the subjects in the malignant-tumor, benign-tumor, and control groups. Patients with malignant tumors underwent second and third phlebotomies one week following the surgery and after the chemotherapy regimen, respectively. MGMT, GST, and protein levels were measured for each serum sample. GST activity of the samples was measured by the method of Habig et al. using l-chloro-2-4 dinitrobenzene (CDNB) as substrate. MGMT activity was measured by the transfer of radio labelled methyl groups from a prepared MG-DNA substrate to the enzyme fraction of serum. Protein concentration was measured by biuret method. RESULTS: Our work demonstrated that untreated patients with malignant ovarian tumors revealed significantly greater MGMT and GST activities in their sera than did both healthy individuals and patients with benign ovarian tumors, while no significant difference was found between the healthy group and the patients with benign ovarian tumors with respect to their sera MGMT and GST activities. GST activity following chemotherapy was significantly lower than the postoperative values preceding chemotherapy. A relationship between sera MGMT and GST activities, tumor histology and pathology was not found in this study. CONCLUSION: Our work suggests the fact that detection of sera MGMT and GST activities is important in diagnostic and therapeutic approaches during the course of ovarian cancer.

Aged↗

PubMed2004

The effect of prostate cancer and antiandrogenic therapy on lipid peroxidation and antioxidant systems.

In living organism, excessive free radicals or oxidative damage which occur as a result of deficient antioxidant defensive mechanisms by the effect of endogenous and exogenous factors, influences especially developmental steps of chemically induced cancers. In our study, plasma malondialdehyde level (MDA) as an indicator of lipid peroxidation, erythrocyte glutathione (GSH) level as an indicator of antioxidant state, glutathione reductase (GSH-Red), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) as an antioxidant enzymes and plasma vitamin E level were detected in patients with prostate cancer (21 males; age, 69.4 +/- 4.8 years) before and after three months of antiandrogenic therapy with goserelin acetate as luteinizing hormone releasing hormone (LHRH) analogue. Healthy people evaluated as a control group (20 males; age, 63.7 +/- 3.9). Erythrocyte GSH levels, the activities of GSH-Red and GSH-Px and plasma vitamin E levels were found significantly low in patients with prostate cancer when compared with the healthy subjects (p < 0.01, p < 0.05, p < or = 0.001 and p < or = 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p < or = 0.001 and p < or = 0.001 respectively). After antiandrogenic therapy erythrocyte GSH level, GSH-Red, GSH-Px activity and plasma vitamin E level were found unchanged. Significant decrease in plasma MDA level and significant increase in erythrocyte GST activity were detected in patient group (p < 0.05 and p < or = 0.01 respectively). The study has revealed the shift in the oxidant-antioxidant balance towards oxidative state in patients with metastatic prostate cancer. Our results showed that antiandrogenic therapy increased in GST activity, decreased in lipid peroxidation.

Aged↗

PubMed2003

DNA damage and antioxidant defense in peripheral leukocytes of patients with Type I diabetes mellitus.

We determined relationship among DNA damage, nitric oxide (NO) and antioxidant defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G-Px) activity of the leukocytes were measured by spectrophotometric kits. Serum glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients, as expected. Differences in measured parameters between controls and patients were assessed in men and women separately. There was no significant difference between patient and control groups in neither men nor women for nitrite level. Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px activities of the leukocytes were found to be decreased in both men and women of patient group as compared to their respective controls. Significant correlations were determined between strand breakage and HbA(1c) (r = 0.37, P<0.05); Fpg-sensitive sites and HbA(1c) (r = 0.59, P<0.01); Fpg-sensitive sites and glucose (r = 0.45, P<0.02); Fpg-sensitive sites and SOD (r = -0.48, P<0.02); HbA(1c) and SOD (r = -0.50, P<0.02). In conclusion, impaired antioxidant defense in leukocytes of patients with Type 1 DM may be one of the responsible mechanisms for increased DNA damage in those patients.

Adult↗

PubMed2003

Relation of aging with oxidative protein damage parameters in the rat skeletal muscle.

OBJECTIVES: An increase in oxidative stress may contribute to the development of oxidative protein damage in the aging rat skeletal muscle. Our aim was to reveal protein carbonyl (PCO), advanced oxidation protein products (AOPP), a novel marker of oxidative stress, and protein thiol (P-SH) levels as markers of protein oxidation, as well as lipid hydroperoxide (LHP) levels as a marker of lipid peroxidation, and relation of nitrotyrosine (NT) levels with these markers in skeletal muscle tissue of young, adult, and old male Wistar rats. DESIGN AND METHODS: In the present study, we investigated the relation between aging and oxidative protein damage parameters such as PCO, NT, AOPP, and P-SH, as well as oxidative stress parameters such as total thiol, nonprotein thiol, and LHP in the skeletal muscle tissue of young, adult, and old Wistar rats. RESULTS: PCO and NT levels of old rats were significantly increased compared with those of young and adult rats. Skeletal muscle AOPP levels were significantly increased in old rats compared with those of adult rats. P-SH levels were significantly decreased in old rats compared with those of young rats. CONCLUSIONS: The finding that the increase in PCO levels of young vs. old group was more significant than that of adult vs. old group may suggest that PCO formation is an early specific marker of aging process in skeletal muscle. In addition, increased levels of nitrotyrosine in the skeletal muscle of the old rat group may be a novel specific marker of oxidative protein damage in the aging muscle. The absence of correlation between oxidative protein damage markers mentioned above and LHP levels may indicate that protein oxidation and lipid peroxidation in the aging rat skeletal tissue are two distinct mechanisms.

Aging↗

PubMed2003

O(6)-methylguanine DNA methyltransferase activity in diabetic patients.

In the present study, we evaluated O(6)-methylguanine-DNA methyltransferase (MGMT) activity in diabetic patients. The study was performed on 27 patients with Type 1 diabetes, and 42 with Type 2 diabetes. Patients with complications were excluded from the study. 36 non-diabetic volunteers, non-smokers who do not consume alcoholic beverage, were chosen from the medical staff as control subjects. MGMT activity was measured by the transfer of radiolabeled methyl groups from a prepared methylguanine-DNA substrate to the enzyme fraction of leukocyte extract. Leukocyte MGMT activity was significantly reduced in both Type 1 and Type 2 diabetes patients as compared with control subjects (P<0.001). The present study demonstrates decreased MGMT activity in leukocytes from patients with Type 1 and Type 2 diabetes.

Adult↗

PubMed2003

Relation between bladder cancer and protein oxidation.

DNA, protein oxidation and lipid peroxidation possess a major impact in carcinogenesis. Also, inflammatory and oxidative events have remarkable importance in bladder cancer. Thus, in this study total protein, protein carbonyl, nitrotyrosine, thiol residues, non-protein thiols, lipid peroxidation, and also, because of their relations to the above parameters, iron and iron binding levels have been investigated in patients with bladder cancer and in control group. Statistical evaluation of the results demonstrated significantly lower plasma protein levels in the patients with bladder cancer, as compared to the healthy control group. Serum iron levels in patients with invasive bladder cancer were found to be significantly lower when compared with non-invasive group. Protein carbonyl groups were remarkably higher in bladder cancer patients than in healthy controls. Patients with bladder cancer were demonstrated to have significantly lower levels of total thiol groups and protein-bound thiol groups as compared to healthy controls. Protein-bound thiol groups in patients with invasive bladder cancer revealed a more significant decline, than in non-invasive group.

Aged↗

PubMed2003

Increased formation of 8-hydroxy-2'-deoxyguanosine in peripheral blood leukocytes in bladder cancer.

INTRODUCTION: Reactive oxygen species-induced damage to DNA plays a major role in carcinogenesis. METHODS: In order to estimate the level of oxidative damage in bladder cancer, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was determined in DNA isolated from peripheral blood leukocytes of healthy adults and patients with superficial transitional cell carcinoma. Patients with transitional cell carcinoma of the bladder and control individuals were similar in age. In this study, the level of 8-OHdG in DNA in male subjects was measured by the high-performance liquid chromatography-electrochemical detector method. RESULTS: The 8-OHdG levels in DNA from leukocytes of bladder cancer patients were significantly higher than those in controls. CONCLUSION: Reduction of oxidative stress is thought to be a very important measure for primary prevention of bladder cancer.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2003

Evaluation of O6-methylguanine DNA methyltransferase activity in patients with gastric cancer.

O6-Methylguanine DNA methyltransferase (O6-MGMT) reverses DNA alkylation damage produced alkylating agents. O6-MGMT is also a major determinant of cellular resistance to adjuvant chemotherapy with alkylating drugs. O6-MGMT activity was measured in samples from patients with gastric cancer, including tumor, adjacent normal appearing mucosa, and peripheral blood leukocytes (PBL). O6-MGMT activity of PBL from healthy individuals was evaluated as control. There was no significant difference between controls and patients for O6-MGMT activity in PBL. O6-MGMT activity was significantly increased in tumor tissue. Tumor O6-MGMT activity was found to be independent from tumor subgroups and tumor grade. A positive correlation was determined between O6-MGMT activity in tumor and in circulating PBL. The results indicate that O6-MGMT, a defense protein against alkylating agent-mediated carcinogenesis, increased in gastric tumors. This may explain the low response rate to drug combinations, including chloroethylnitrosoureas, exhibited by patients with gastric cancer.

Adult↗

PubMed2002

Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes.

The first aim of the present study was to examine the relationship between reduced glutathione (GSH) level, a powerful cellular antioxidant, and oxidative damage to DNA; and secondly, to see the effect of glycemic control on oxidative DNA damage in type 2 diabetics. We determined GSH level and, using the comet assay, formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites which indicates oxidised guanine in freshly isolated blood from age-matched type 2 diabetics and controls. We found significant differences between men and women in the control group for both GSH and Fpg-sensitive sites. Therefore, we compared the controls and type 2 diabetics separately in men and women. GSH level of whole blood was found to be lower, Fpg-sensitive sites in leukocytes was found to be higher in the both type 2 diabetic men and women, as compared with their respective controls. When the diabetic group was divided into two groups as well-controlled diabetics and poorly-controlled diabetics with respect to glycosylated haemoglobine levels, it was found that Fpg-sensitive sites was significantly higher in the poorly-controlled diabetics than in the well-controlled diabetics in both the men and women. GSH level was lower in the poorly-controlled diabetics but not significantly. Fpg-sensitive sites were found to be moderately correlated with both glycosylated haemoglobine and GSH, and weakly correlated with glucose. Data indicate that decreased GSH level may be a contributory factor for enhanced oxidative DNA damage in type 2 diabetics; and chronic hyperglycemia derived from poorly-controlled diabetic conditions may induce oxidative DNA damage in these patients.

Comet Assay↗

PubMed2002

Susceptibility of glutatione and glutathione-related antioxidant activity to hydrogen peroxide in patients with type 2 diabetes: effect of glycemic control.

OBJECTIVES: The aim of the present study was to examine the susceptibility of glutathione (GSH) and glutathione related antioxidant enzymes to oxidation in type 2 diabetic patients with and without glycemic control. DESIGN AND METHODS: Erythrocyte glutathione level and activities of glutathione peroxidase (G-Px), glutathione reductase (G-Red) and glutathione S-transferase (GST) in controls, well controlled and poorly controlled type 2 diabetics were measured by spectrophotometric assays before and after the incubation in vitro with H2O2. RESULTS: GSH level, G-Px and G-Red activities decreased but GST activity increased in the erythrocytes from all the groups after the incubation with H2O2. Percentage of decrease in GSH was independent from glycemic control, whereas the percentage of decreases in G-Px and G-Red was related to glycemic control. The percentage of increase in GST was found to be independent from diabetes. CONCLUSIONS: GSH and GSH-related antioxidant enzymes in human erythrocytes are susceptible to oxidation, particularly, G-Px and G-Red which were found to be more susceptible to oxidation in erythrocytes from poorly controlled type 2 diabetic patients.

Analysis of Variance↗

PubMed2002

Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme activities in diabetic rats.

1. Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. Recently, alpha-lipoic acid (ALA) has gained considerable interest as an anti-oxidant. Various studies have indicated the anti- oxidant effects of ALA and its reduced form dihydrolipoic acid. Therefore, it appears that these compounds have important therapeutic potential in conditions where oxidative stress is involved. The aim of the present study was to investigate the effect of ALA supplementation on lipid peroxidation and anti-oxidant enzyme activities in various tissues in diabetic rats. 2. Male Wistar rats were divided into three groups. Diabetes was induced by streptozotocin (STZ) injection in the two groups of rats to be supplemented and not to be supplemented with ALA. Another group of rats, which received saline injection, formed the control group. After 5 weeks of diabetes, rats were killed. In order to assess the redox status of various organs in the diabetic and control rats, thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (G-Px) and glutathione reductase (G-Red) activities were determined in the liver, pancreas and kidney. 3. In both diabetic groups, TBARS levels and SOD activity were increased in the liver and pancreas, G-Px and G-Red activities were increased in the kidney and GSH levels were decreased in all organs compared with controls. In the ALA- supplemented group, TBARS levels were decreased, GSH levels were increased in the liver and pancreas, SOD activity was decreased in the liver, G-Px activity remained unchanged in all tissues and G-Red activity was increased in the pancreas compared with the diabetic group that did not receive ALA supplementation. 4. In conclusion, ALA supplementation has disparate effects on the redox status of different organs. These data are not sufficient for confirmation the beneficial effects of ALA supplementation on the redox status of various organs in diabetic rats.

Animals↗

PubMed2002

Glutathione S-transferase and O6-methylguanine DNA methyl transferase activities in patients with thyroid papillary carcinoma.

Alkylating agents, which are metabolized by glutathione S-transferase (GST), have an important role in the etiology of cancer by forming mutagenic DNA adducts. Previous studies have shown that DNA repair protein, O6-methylguanine DNA methyltransferase, repairs these mutagenic DNA adducts and its activity is correlated with the resistance of human tumors to alkylating agent-based anti-cancer drugs. However, little is known about GST and O6-methylguanine DNA methyltransferase activities in patients with thyroid cancer in vivo. We measured the activities of GST and O6-methylguanine DNA methyltransferase in the leukocytes from patients with papillary thyroid carcinoma and healthy controls. The GST activity was significantly higher in men than in women, and it was negative correlated with age in men whereas it was unchanged in women in the control group. Both GST and O6-methylguanine DNA methyltransferase activities were significantly increased in the patient group. There were no age and sex-related changes in the O6-methylguanine DNA methyltransferase activity in both the control and patient groups. These results suggest that leukocyte GST and O6-methylguanine DNA methyltransferase activities were increased with thyroid cancer. This may be related to the resistance to chemotherapy exhibited by patients with thyroid cancer.

Adult↗

PubMedDate not supplied

Effect of alpha-lipoic acid supplementation on markers of protein oxidation in post-mitotic tissues of ageing rat.

In the present study, we investigated whether DL-alpha-lipoic acid (LA) supplementation could have prooxidant or antioxidant effects on oxidative protein damage parameters such as protein carbonyl (PCO), nitrotyrosine (NT), advanced oxidation protein products (AOPP), and protein thiol (P-SH), as well as oxidative stress parameters such as total thiol (T-SH), non-protein thiol (Np-SH), and lipid hydroperoxide (LHP) in the brain and the skeletal muscle tissue of aged rats. PCO, and NT levels were increased, AOPP and P-SH levels were not changed in the brain tissue of aged rats given LA supplementation. On the other hand, TSH, Np-SH, and LHP levels were decreased in the brain tissue of aged rats given LA supplementation. The levels of the same parameters were not significantly different in the skeletal muscle tissue of aged rats given LA supplementation. The increased levels of protein oxidation markers such as PCO, and NT in the brain tissue of LA-supplemented aged rats compared with non-supplemented aged rats may suggest that oxidative protein damage is increased in LA-supplemented aged rats. We assume that an explanation for our findings regarding LA supplementation on protein oxidation markers in the brain tissue of aged rats may be due to the prooxidant effects of LA. Depending on post-mitotic tissue type and dosage of LA, the prooxidant effects of LA supplementation, should be considered in future studies.

Aging↗

PubMedDate not supplied

Decrease in mitochondrial oxidative protein damage parameters in the streptozotocin-diabetic rat.

BACKGROUND: Many authors have shown that hyperglycemia leads to an increase in oxidative protein damage in diabetes. The aim of this study was to reveal the susceptibility of mitochondria from liver, pancreas, kidney, and skeletal muscle of diabetic Sprague-Dawley rats, a model of type 1 diabetes, to oxidative protein damage. METHODS: Mitochondrial fractions were obtained by differential centrifugation. To show the effect of hyperglycemia in promoting oxidative protein damage, we determined mitochondrial protein carbonyl, total thiol, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels. The levels of the studied markers, except nitrotyrosine, were determined by colorimetric methods. Nitrotyrosine levels were measured by ELISA. All values were compared with those of the controls by using the Mann-Whitney U-test. RESULTS: Nitrotyrosine and lipid hydroperoxide levels were decreased and other parameters were not changed in liver mitochondria of diabetic rats. Protein carbonyl, nitrotyrosine, advanced oxidation protein products, and lipid hydroperoxide levels were decreased and total thiol levels were not changed in pancreas mitochondria of diabetic rats. Only advanced oxidation protein products and lipid hydroperoxide levels were decreased in kidney mitochondria of diabetic rats. The levels of the same parameters were not significantly different in muscle mitochondria of diabetic rats. CONCLUSIONS: The decrease in mitochondrial oxidative protein damage in diabetes may correspond to either an increase in antioxidant defense mechanisms or a different adaptive response of the cells to the increased extramitochondrial oxidative stress in diabetes. The mitochondrial oxidative protein damage-lowering mechanisms in diabetes remain to be clarified.

Animals↗